Efficacy Evaluation of Novel Therapeutics Targeting TSLP or TSLPRDrug Candidates Using TSLP/TSLPR Double Humanized Mouse Model on BALB/c Background 4786

Abstract Description Yuxi Zhang1, Juan Liang1 GemPharmatech Co.Ltd., 12 Xuefu Road, Jiangbei New Area, Nanjing, 210061, China1; Thymic stromal lymphopoietin (TSLP) is an IL-2 family cytokine produced by epithelial and stromal cells in response to pathogens in the lung, skin, and gut. It regulates immunity at barrier surfaces by promoting a type 2 polarizing phenotype in TSLPR-expressing cell lineages. GemPharmatech developed a double humanized mouse strain on the BALB/c background that expresses human TSLP and TSLPR instead of the mouse homologues. Human TSLP was found to increase in double KI mice following MC903 stimuli. Mouse CCL17(also known as TRAC), which can be produced by dendritic cells, was updated by treatment with human TSLP in DCs derived from homozgotes,This suggests that the human TSLP/TSLPR system is functional in mice. In BALB/c-hTSLP/hTSLPR mice, MC903 induced AD-like phenotypes, including skin lesions, reductions in skin thickness, increased dermatitis scores, elevated inflammatory cytokines, and histopathological signs. Tezepelumab, an approved monoclonal antibody against TSLP, as well as other therapeutic antibodies that target TSLP, significantly alleviated the phenotypes induced by MC903.In addition, in both the OVA- and HDM-induced asthma models, we found anti-TSLP antibody significantly reduced the infiltration of eosinophils and other lymphocytes in the lung. Topic Categories Basic Autoimmunity (BA)